Trial Information

I. To determine the overall objective response rate (RR) to vorinostat in patients with metastatic uveal melanoma harboring a GNAQ or GNA11 mutation.

SECONDARY OBJECTIVES:

I. To determine the overall survival (OS) of these patients. II. To determine the progression-free survival (PFS) of these patients. III. To determine the tolerability of vorinostat in patients with metastatic uveal melanoma.

IV. To assess for changes in pathways, such as the mitogen-activated protein kinase (MAPK) pathway, with treatment.

OUTLINE:

Patients receive vorinostat orally (PO) twice daily (BID) for 3 days weekly for 4 weeks. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 12 weeks.

Inclusion Criteria:

- Patients must have metastatic histologically or cytologically confirmed uveal melanoma (if histologic or cytologic confirmation of the primary is not available, confirmation of the primary diagnosis of uveal melanoma by the treating investigator can be clinically obtained, as per standard practice for uveal melanoma)

- Patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

- Patients must have experienced disease progression on their prior therapy, in the opinion of the treating investigator

- Tumor GANQ, GNA11, and BAP1 mutational status must be determined on all patients; if initial testing is performed locally or not available, Memorial Sloan-Kettering Cancer Center (MSKCC) patients must consent to provide a tumor block or unstained slide to MSKCC for central review of mutational status; if tissue is not available, a pre-treatment biopsy will be necessary for eligibility

- Patients enrolled at Vanderbilt University Medical Center may have GNAQ and GNA11 mutational status determined on a Clinical Laboratory Improvement Act (CLIA)-approved assay at Vanderbilt University Medical Center or MSKCC; tissue must be sent to MSKCC for BAP1 mutational status determination

- The determination of mutational status may be performed retrospectively and will not delay patient treatment on study as long as tissue is available for molecular analysis

- No patients with active or untreated brain metastases; treated brain metastases must have been stable for at least 2 months

- Ability to understand and the willingness to sign a written informed consent document

- Women of child-bearing potential must agree to use effective contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation

- Pregnant women are excluded from this trial; breastfeeding should be discontinued if the mother is treated with vorinostat

- Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of vorinostat administration

- No history of allergic reactions attributed to compounds of similar chemical or biological composition to vorinostat

- Human immunodeficiency virus (HIV)-positive patients on combination chemotherapy will be eligible unless the CD4 count is < 200 cells/mm^3 within one month of study enrollment

- At least 3 weeks must have elapsed since the last dose of systemic therapy

- At least 6 weeks must have elapsed if the last regimen included carmustine (BCNU) or mitomycin C

- At least 6 weeks must have elapsed if the last regimen included an anti-CTLA4 antibody

- No patients who are receiving any other investigational agents

- Patients receiving histone deacetylase (HDAC) inhibitors or compounds with HDAC inhibitor-like activity, such as valproic acid, are ineligible; patients who have received such agents may enroll on this study after a 14-day washout period

- Patients on warfarin will be excluded from the trial if they cannot be switched to an acceptable alternative medication (i.e., low-molecular weight heparin [LMWH])

- No concomitant anti-cancer chemotherapy or other systemic drugs; palliative radiation therapy will be allowed as long as the patient meets all other eligibility criteria

Outcome Measure:

Outcome Description:

For this study a two-stage design will be used to evaluate objective response. At the final analysis, response will be classified by type and duration and 95% confidence intervals, adjusted for the interim looks, will be calculated.

Outcome Time Frame:

Up to 1 year

Safety Issue:

No

Principal Investigator

Richard Carvajal

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-00860

NCT ID:

NCT01587352

Start Date:

April 2012

Completion Date:

Related Keywords:

Metastatic Intraocular Melanoma

Recurrent Intraocular Melanoma

Melanoma

Uveal Neoplasms

Name

Location

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